Serum albumin, a protein with a molecular weight of about 6.6×104 Da, consists of 585 amino acid residues and has an elliptic shape. It accounts for about 60% of the total proteins, is most abundant in plasma and is synthesized in the liver. It participates in maintenance of osmotic pressure of plasma collagen, counteraction of poison and maintenance of acid-base equilibrium. It also plays a role in transporting numerous drugs or chemical substances by binding thereto non-specifically.
Such albumin is formulated into an albumin preparation for use in therapy of burn, hypoalbuminemia due to lost of albumin caused by nephrotic syndrome and reduction of capacity for albumin synthesis, hemorrhagic shock, and the like. An albumin preparation, which includes Plasma Protein Fraction (PPF), is a protein preparation that contains as high a level of a protein as 4.4 to 25%, among which albumin accounts for 80% or more, or 96% or more. Its volume per preparation is also as large as 20 to 250 mL. Thus, a large quantity and volume of a protein needs be handled for production of an albumin preparation.
On the other hand, there is no denying a possibility that a protein, in particular a protein from the living body, more specifically a protein from blood, might be contaminated with various viruses such as AIDS virus, various hepatitis viruses, and human parvovirus B19. Accordingly, for production of a medicament using these proteins as a starting material, it is indispensable to incorporate a step of sufficiently removing or inactivating viruses.
For inactivation of viruses, a possibility of whose contamination in a preparation from blood, i.e. a blood preparation, is not denied, heat treatment has commonly been used. Alternatively, a solvent-detergent (SD) approach may also be used for inactivation of viruses in which special solvents and detergents are used (see Japanese Patent Publication No. 051116/1985). Viruses may also be removed by affinity chromatography, or ion exchange chromatography (see Developments in Biological Standardization, Vol., 81, 199-209 (1993)). However, all these approaches have both merits and demerits and each of individual approach alone would not likely provide complete inactivation or complete removal of viruses. Thus, it is accepted that plural approaches may effectively be used in combination.
An albumin preparation, a target of the present invention, has been subject to inactivation/removal of viruses by heating in a liquid state (at 60° C. for 10 hours) and alcoholic fractionation and its safety has been proved by its clinical use for over fifty years. However, in view of further promotion of safety, as a measure for inactivation/removal of pathogens such as viruses not being inactivated/removed even through the above processes or unknown pathogens such as viruses that have not yet been found, an approach for removal of these pathogens has been investigated using filtration with a virus-removing membrane. However, no such filtration with a virus-removing membrane has been practically introduced for production of an albumin preparation on a commercial basis.